This invention relates to biochemistry, and to anti-viral agents for use as preventive agents, to reduce the risk that a previously uninfected person will become infected by sexually-transmitted viruses (such as genital herpes, HIV/AIDS, hepatitis, or papilloma viruses) or other microbial diseases (such as syphilis, gonorrhea, or chlamydia).
The anti-viral activity of zinc salts and zinc ions, when applied topically to mucous membranes inside the body, is discussed in a number of prior patents issued to George Eby, involving lozenges taken by mouth (e.g., U.S. Pat. Nos. 4,503,070 and 5,409,905).
Various additional US patents involving the use of zinc salts in genital lubricants, for use during sexual intercourse, have been issued to Patrick Kelly, the same inventor herein. Those patents include U.S. Pat. Nos. 5,208,031 (May 1993), 5,482,053 (January 1996), 5,624,675 (April 1997), and 5,980,477 (November 1999). The contents of those patents are incorporated herein, as though set forth in full. Published articles describing the inhibition of herpes viruses by zinc salts include Eby and Halcomb 1985, Kumel et al 1990, and Arens and Travis 2000.
Novick et al 1996 proposes a specific molecular mechanism that would allow zinc to exert a substantial anti-viral effect, outside of cells and membranes. In this mechanism, positively charged zinc ions (Zn++), which are released when a water-soluble zinc salt is dissolved in water, are attracted to negatively-charged canyons, in the surface proteins that are present on the surfaces of virus particles and cells. Since opposites attract, the positively-charged zinc ions settle into the negatively-charged protein canyons, and occupy those canyons.
This disrupts and alters the binding conformation and affinity of the surface proteins, in a manner comparable to shoving a toothpick or paperclip into a keyhole. On a visible level, as long as a foreign object remains jammed in a keyhole, it will be impossible to fit the real key into that keyhole. On a molecular level, as long as positively-charged zinc ions occupy and disrupt negatively-charged canyons in the surface proteins that enable virus particles to bind to certain types of cells, virus particles that have been exposed to an adequate concentration of zinc ions will not be able to bind to and infect cells having the surface proteins that are normally targeted by the virus particles.
Another potential mechanism that may help explain zinc""s anti-viral activity should also be noted. Zinc ions are known to form relatively stable and strong crosslinking bonds with cysteine and histidine residues, in proteins. In nature, these crosslinking bonds normally cause two different strands of a single protein to become bound to each other, and they are highly important in establishing and stabilizing the three-dimensional conformations of many types of proteins, including so-called xe2x80x9czinc finger proteinsxe2x80x9d.
In a situation involving a lubricant or rinse that contains zinc ions in a concentration that is thousands of times greater than can be established in natural biological fluids, the same types of crosslinking bonds, made in very large numbers by a huge surplus of free zinc ions, can collectively provide sufficient strength to randomly bind viral particles to each other, and to proteins on the surfaces of dead and dying (xe2x80x9cpyknoticxe2x80x9d) cells that are being sloughed off continuously by the epidermal and epithelial membranes of the penis, vagina, and rectal cavity. This can effectively prevent the entangled virus particles from infecting viable cells and establishing an active infection.
In addition, zinc is known to have skin-protective and mild wound-healing properties. Zinc compounds such as zinc oxide and zinc acetate are present in hundreds of ointments and creams, including nearly every type of ointment sold and used today for treating diaper rash, bedsores, etc. Published articles that describe the activity of zinc in promoting wound healing and skin closure, and in stabilizing cell membranes and multi-cellular membranes, include Chvapil 1973 and 1976, Agren 1990, Bray and Bettger 1990, Hennig et al 1992, Kaszuba and Hunt 1990, Mahadevan, et al 1990, Pasternak 1990, Pasternak et al 1992, and Hennig et al 1992. In addition, Chvapil et al 1978 and 1980 reported that when certain zinc salts were added to certain contraceptive products, the zinc seemed to reduce detectable signs of irritation and inflammation caused by the other agents.
Williams 1980 indicated that zinc salts had mild contraceptive activity in rabbits. Although zinc""s level of contraceptive potency in that report was insufficient to support commercialization and public use, it also reportedly increased the contraceptive potency of nonoxynol, a widely used spermicide, in those tests.
Despite those steps forward, various problems have blocked any actual public or commercial use of zinc in genital lubricants. As of the filing date of this application, in November 2001, there are no genital lubricant products (either in a stand-alone liquid or gel, or pre-packaged with a condom) which are on the market and available to the public, which contain a zinc salt as an anti-viral additive. One of the major problems which has hindered the licensing and commercialization of genital lubricants with zinc salts has been an unending dispute over the efficacy of zinc lozenges; for every report which describes a positive result, another report describing a negative result has also appeared. In addition, for various reasons (which seem to center around profit potentials, unproven technology, and the difficulty and expense of carrying out human clinical trials of a size needed to establish clear evidence that is strong enough to satisfy the U.S. Food and Drug Administration, and comparable agencies in other countries), the major pharmaceutical companies of the world have refused to make serious commitments to funding research on any types of topical genital microbicides. This assertion can be borne out by various news articles and industry surveys distributed by the Alliance for Microbicide Development (Silver Spring, Md.; www.microbicides.org), and other organizations working on topical microbicides intended for use on the genitals, such as The Population Council (New York City; www.popcouncil.org) and CONRAD (Contraceptive Research and Development; Arlington, Va.; www.conrad.org)
Accordingly, one object of this current invention is to disclose a novel formulation for using a rinse-type formulation containing a suitable zinc salt, either shortly before coitus or shortly following coitus, to reduce the risk of infection by sexually transmitted viruses.
Another object of this patent application is to further expand the set of patent rights which can be used to help support and justify funding for the scientific research that will be necessary to establish a clear scientific consensus on whether a suitable zinc compound, in a topical formulation applied to one or more genital surfaces, is indeed a safe, effective, and useful anti-viral agent for reducing the risk of infection by sexually transmitted viruses.
This invention discloses the use of an aqueous rinsing liquid which contains a water-soluble zinc salt at an anti-viral viral concentration, and which is designed to be used as a genital rinsing and cleansing agent, shortly before and/or shortly after intercourse, comparable to a douche or enema. Unlike a lubricant gel or liquid, which will contain a lubricating agent with an affinity for skin (such as glycerin), this type of rinsing liquid will be designed to not leave behind any substantial residue, other than zinc ions. This type of xe2x80x9cperi-coitalxe2x80x9d rinse (i.e., intended for pre-coital or post-coital use) will leave behind a residue of positively-charged zinc ions. Due to electrostatic attraction, these Zn++ ions will cling to negatively-charged canyons and other negative xe2x80x9cbinding sitesxe2x80x9d in proteins that are exposed and accessible on the surfaces of cells or virus particles. The binding of Zn++ ions to negatively-charged binding sites in these surface proteins will alter and disrupt the ability of viruses (including herpes and HIV, and probably hepatitis and papilloma viruses as well) to bind to and infect human cells. Accordingly, a peri-coital rinse containing a water-soluble zinc salt can reduce the risk of infection, by sexually transmitted viruses, in a person who is not previously infected.
In addition, due to the skin-healing properties of zinc, a zinc-containing peri-coital rinse can also help promote and accelerate the healing and closure of microabrasions, lesions, and other breaches or deficits in genital skin or mucous membranes. Since intact skin plays a major role in fighting off infections, genital abrasions and lesions can greatly increase the risk of viral and other infections.